Imizekelo yezilwanyana zotywala kunye nokuxhomekeka kweziyobisi (2013)

Ukusetyenziswa kweziyobisi kunempilo. Kwiminyaka yokugqibela ye-50, uluhlu olubanzi lweendlela luye lwenziwa ukubonisa imiba ethile yokuziphatha kwabantu abathatha iziyobisi kwaye banegalelo elikhulu ekuqondeni isiseko se-neurobiological sokusebenzisa iziyobisi kunye neziyobisi. Kule minyaka mibini idlulileyo, kuphakanyiswe imodeli ezintsha kumzamo wokubamba ezona zinto ziqinisekileyo zokuziphatha-okufana nokuziphatha kwizilwanyana zaselebhu. Injongo yoqwalaselo lwangoku kukubonelela ngesishwankathelo seenkqubo zangaphambili zokusetyenziswa gwenxa kweziyobisi kunye nokuxhomekeka kwaye sichaze inkqubela phambili eyenziweyo ekufundeni ngakumbi iinkalo ezithile zokuziphatha okubi kwizilwanyana.

intshayelelo

Ukusetyenziswa kweziyobisi gwenxa ngumceli mngeni omkhulu kwezentlalo, kungekuphela ngenxa yeziphumo ezinxulumene nezempilo kodwa nangenxa yefuthe labo kwezentlalo nakwezomthetho kuluntu. Isiyobisi yinto eyenzeka ebantwini engenakuphinda iveliswe ngokutsha kwindawo yokusebenzela ngaphandle kokuthintelwa kuthintelo. Nangona kunjalo, ezinye zeempawu zokuziphatha zesi sifo zinokumodareyithwa ngokufanelekileyo kwizilwanyana zaselebhu. Ngale ndlela, uluhlu olubanzi lweendlela luye lwaphuhliswa ukubonisa imiba ethile yokuziphatha ngokuthatha iziyobisi. ^1,2 Amandla okufunda kwezi ndlela zokuziphatha kwizilwanyana anegalelo ekuqondeni isiseko se-neurobiological sokuthathwa kweziyobisi kunye neenkqubo zobuchopho ezithatha inxaxheba kumvuzo wezinto zengqondo. Nangona kunjalo, eyona njongo iphambili yophando lokusebenzisa gwenxa iziyobisi kukufumana iindlela zokulutha; Ke, kule minyaka ingamashumi amabini idlulileyo, kuye kwenziwa izindululo ezintsha kwimizamo yokubamba izinto ezizezona zilungileyo zokuziphatha okunje ngeziyobisi zaselebhu. ²

Injongo yoqwalaselo lwangoku kukubonelela ngesishwankathelo seenkqubo zangaphambili zokusetyenziswa gwenxa kweziyobisi kunye nokuxhomekeka kwaye sichaze inkqubela phambili eyenziweyo ekufundeni ngakumbi iinkalo ezithile zokuziphatha okubi kwizilwanyana.

Imodeli yebhotile ekhethiweyo yasimahla

Imodeli yebhotile ekhethiweyo yasimahla yindlela engalawulekiyo yokulawula umda kumgaqo wolawulo kwaye isetyenziswa rhoqo kuphando lweziyobisi. Le ndlela ayisebenzi, itheknoloji ilula, kwaye isebenzisa indlela yolawulo apho abantu batyale i-ethanol. Iindlela zokuzilawula ze-Oral ethanol zilawula ubuso kwaye zisebenza njengemodeli yokusela kotywala boluntu, kuba izifundo zinokukhetha ukusela utywala kunye nesixa esimiselweyo ngexesha lokuboniswa. Le modeli inokusetyenziselwa ukuphanda iziphumo ezifutshane okanye zexesha elide zokuvezwa kwi-ethanol, kunye neendlela ze-neurobiological ezinxulumene nokusetyenziswa gwenxa kotywala kunye notywala. ¹ Ukongeza, ezi ndlela zinokuba luncedo nakwindlela yokonyango ekuthatheni isiselo esinxilisayo, esibonisa ukubaluleka kwaso. ³

URichter kunye neCampbell, ⁴ I-in1940, baba ngabokuqala ukunika ingxelo yokuba iirabhu zelebhu ngokuzithandela zitya i-ethanol. Babonisa ukuba iigundane zabela ukusela kwabo phakathi kwebhotile yamanzi kunye nebhotile enesisombululo se-ethanol, esivela kuvavanyo lwebhotile ezimbini. Ukuselwa kotywala ngeentonga kuya kuvavanywa rhoqo kule ndlela, apho kufumaneka isiselo esinxilisayo kunye namanzi kwizindlu zabo zasekhaya, ngokutya okukhoyo kwintengiso yethutyana. Ngenye indlela, izilwanyana zinokufikelela ngokufanayo emanzini kunye nezinye iibhotile ezininzi eziqukethe ukohluka kwe-ethanol. Indlela yokukhetha ngokukhululekileyo, usebenzisa ibhotile enye okanye ezingaphezulu ukubonelela nge-ethanol, iluncedo ekuqikeleleni ngokuzithandela nasekuzenzeleni ukutya, njengoko isilwanyana singanyanzeliswa ukuba sisele amanzi. ⁵ Ngokubanzi, kubonisiwe ukuba ukusela utywala kuyanda xa inani eliphezulu lezisombululo ezizezinye zivezwa. ⁶

Ukulinganiswa kokutya kwe-ethanol kuvame ukwenziwa ngokulinganisa amanzi kunye neebhotile ze-ethanol kanye ngeyure nganye ye-24. Ukhetho lotywala luchazwa ngokwemigqaliselo ye-ethanol ye-g kwi-ethanol / kg ubunzima bomzimba / ngosuku, kunye nepesenti yolwelo olugcweleyo. ⁷ Nangona kunjalo, iimpembelelo ze-ethanol zixhomekeke kungekuphela kwixabiso elipheleleyo le-ethanol echithezwe ngumqolo okanye iigundane ngaphakathi kweeyure ze-24 kodwa nakwikhosi yexesha kunye nephethini yokusela, ukulinganiswa ngokulandelelana kweendlela zokufumana isisombululo se-ethanol kunye nesixa isetyenziselwe indlela yokusela ⁸ Ukusetyenziswa kwezi ndlela zozibini kuyinjongo yokuphelisa umkhethe kwizilwanyana ngokubonakala kotywala obuphezulu ngenxa yomzimba omncinci okanye ukutyeba kakhulu. ⁷

Iiringi ezifundwe phantsi kwemeko yokufikelela ngokuqhubekekayo kwizisombululo ngokubanzi aziseli ngokwaneleyo ukufikelela kwi-ethanol egxilwe ngaphezulu kwe-80 mg / dL (iigundane) okanye i-100 mg / dL (iimpuku), ezinokuthathwa njengotywala kakhulu kwiigundane kunye neempuku, ngokwahlukeneyo . ^9,10 Kubonakalisiwe ukuba ukusetyenziswa kwe-ethanol kukhuphuka ngokufikelela ngexesha. Imodeli yokufikelela ngokuthe ngcembe (lonke elinye ixesha le-24-iyure) kwi-ethanol kwiigundane kukhokelele kwiipatheni zokusela ukusetyenziswa kwe-ethanol ephezulu (i-9 g / kg / ngosuku). ¹¹ Ubungqina obuninzi bucacisa ukuba ukuvumela ukufikelela kwi-ethanol kwisiseko sexeshana kunokubonelela ngeendlela zokwenza umthambo. ¹²

Ukugxininiswa kotywala ngomnye umba obalulekileyo kwezi nkqubo, kuba ukujolisa kancinci kunokusela ngenxa yokuncasa kunambitheka kamnandi kunye nokujolisa okuphezulu ngenxa yokuthanda ukunambitha. Ke, ihlala ithathelwa ingqalelo yokuba ugxininiso lwe-ethanol engaphantsi kwe-4% (v / v) aluzukudala uxinzelelo lwegazi luphezulu ngokwaneleyo ukuze lubangele iziphumo ezichaphazelekayo zekhemikhali, kunye nokuba uxinzelelo kuluhlu lwe8-12% ngumgangatho ofanelekileyo wokusetyenziswa ziintonga. . Njengoko uninzi lweentwala zeentwala ngokufuthi zingaseli kwizisombululo ezixineneyo ze-ethanol, iinkqubo ezininzi ziye zenziwa ukuqeqesha iintonga ukuba zisebenze ngokwasemthethweni izixa ezifanelekileyo zotywala, kubandakanya nokuboniswa kokunyuka kwe-ethanol kunye nokuthintelwa kwexesha lokunyanzelwa. ukubonakaliswa kwi-ethanol. ^1,6

Enye indlela yokwandisa ukusetyenziswa kwe-ethanol kubandakanya ukuxhaphaka kwexabiso lokukhuthaza lesisombululo ngokwandisa ukuqina kwaso; oku kunokufezekiswa ngokongeza iarhente yokuncamathisela okumnandi, enje nge-sucrose okanye iscalcharin, kwisisombululo se-ethanol. Ukuxinwa kwe-sweetener inokugcinwa rhoqo okanye ngokuthe ngcembe kuncitshiswe ngexesha lokuvezwa. ¹²

Kubalulekile ukuba uqaphele ukuba ukusukela emva kwexesha le-1940s, i-rodent strins zenziwe ngokukhetha okukhethiweyo kokukhetha okuphezulu kwe-ethanol. Ukususela ngoko, iintlobo ezithile zeempuku kunye neempuku ziye zikhethwe ngokukhethekileyo kwi-ethanol ephantsi ekhethiweyo kwaye isetyenziswe kumakhulu ezipapasho kwintsimi yokusetyenziswa kotywala. ¹³

Ukutya okuselwelo

Kwisifundo esiqhelekileyo sikaLieber kunye noDeCarli, ¹⁴ I-ethanol yongezwa kubuninzi obuphezulu bokutya okuyi-fluid okukuphela kwesondlo, ngokunyanzela iigundane okanye iimpuku ukuthatha i-ethanol equkethwe kukutya. Ukutya kwaqulunqwa ngendlela yokuba ixabiso layo lesondlo ligqithise iipropathi zotywala kwaye zavelisa isiselo esinxilisayo ukuya kuthi ga kwi-14-16 g / kg / ngosuku.

Kuphando olwenziwe kutshanje olwenziwe nguGilpin et al., ¹⁵ iigundane zavunyelwa ukufikelela kwi-ad libitum ukufikelela kwi-9.2% (v / v) i-ethanol-ulwelo lokutya apho i-41% yeekhalori zokutya zazithathwe kwi-ethanol. Ababhali babonisa ukuba intsingiselo yemihla ngemihla ye-9.2% (v / v) yokutya okunxilisayo yotywala yayiyi-79.04 ± 3.64 mL kuyo yonke imihla yokuvavanywa, eyayilingana nokuhlutha kwe-ethanol ye9.52 ± 0.27 g / kg / ngosuku. Iziphumo zokugxininiswa kotywala egazini yayi-352 mg / dL, ilinganiswe iiyure ezimbini emva kokuqala komjikelo wobumnyama, kwaye kufutshane iiyure ze-80 mg / dL 8 emva kokuqala komjikelo wokukhanya. Ke, nangona ukusetyenziswa kokutya okuselwelo kusezantsi ngexesha lesigaba sokukhanya, iigundane ezisetyenziswa ngokwaneleyo ukugcina ukugxininiswa kweotywala egxile kwizonyango. Ukuthathwa kwe-ethanol ngexesha lokuvezwa kokutya okuselwelo kwaye kukwazile ukuphakamisa okusebenzayo utywala kuphendula xa iigundane kuvavanywa ukurhoxa ekutyeni okulamanzi.

Ngaphandle kokukwazi ukuvelisa iqela elithile leempawu ezithile zokurhoxa kwezinye izilwanyana ezinempilo, ^16,17 kunye nokwenza ukuba kufundiswe ukuqiniswa kunye nezinto ezikhuthazayo ze-ethanol, ¹⁵ Indlela yokondla utywala njengenxalenye yokutya okuselulwelo kukhokelela kumanqanaba otywala egazi ahambelana neemeko zeklinikhi kwaye ivumela ukuphindaphinda ukuphindeka kwengxaki ezininzi zengqondo ezibangelwa butywala, ezinje ngesifo esinamafutha esibindi, izifo ezenzeka emzimbeni zotywala, kunye nokunxibelelana I-ethanol eneezinyibiliki zemizi-mveliso, iziyobisi ezininzi ezisetyenziswa ngokufuthi, kunye nezakha-mzimba. ¹⁸

Utywala umsi

Imodeli yokufakelwa inhalation yotywala yaphuhliswa kumzamo wokuzama ukuxhomekeka kwimeko yokuxhomekeka kotywala. ^19,20 Iprothokholi isebenzisa iinkqubo zokunxibisa umphunga wotywala ezifumanekayo kurhwebo ukubhenca iigundane okanye iimpuku kwi-ethanol vapor. Utywala kumphunga wotywala yinkqubo engavuniyo evumela ukuba kulawulwe idosi, ubude bexesha, kunye nephethini yokuveza njengoko kumiselwe ngumvavanyi, kwaye akupheliswanga kukuxelwa kwangaphambili kwesilwanyana ukusela ngokuzithandela utywala. Emva kokupheliswa kokuvezwa komphunga wotywala, izilwanyana zibonisa iimpawu zonyamezelo kunye nokuxhomekeka komzimba kwaye zisenokuvavanywa ngobuninzi bokuziphatha okushukumisayo, ukurhoxa okunamandla- kunye nokuziphatha okuhambelana nokuziphatha. ²¹

UGilpin et al. ¹⁵ ukuveza amagundane kumphunga wotywala kangangeyure ze-4 kunye nokulinganisa ukunxila kotywala kwiimpawu zengqondo kunye neesampuli zegazi eziqokelelwe kwisithambo somsila kwi-30-imizuzwana ngexesha lokuveziswa kweyure ye-4, kunye neeyure ze-8 emva kokupheliswa kotywala. Bafumanise ukuba amanqanaba aphezulu otywala afunyenwe egazini nasengqondweni ngexesha lokuvezwa komphunga yayiyi-208 ± 15 mg / dL kunye ne-215 ± 25 mg / dL ngokulandelelana. Iiyure ezisibhozo emva kokuyeka ukubonakaliswa komphunga wotywala, igazi- kunye namanqanaba obuchopho-botywala babuyile kwisiseko saphambi komphunga, malunga ne0%.

UGilpin et al. ¹⁵ ikwabhengeza amagundane kumphunga ongenakuphela wobushushu bokumisela imeko yomntu apho ukubonakaliswa kotywala kwenzeka kuthotho lweentlelo ezandisiweyo ezilandelwa ngamaxesha okurhoxa. IVapor yathunyelwa kwishedyuli yethuba (nge-6: 00 pm, off at 8: 00 am) isithuba seeveki ze-4. Ukuchaphazeleka okungapheliyo kumphunga ongenamkhethe kuphakamisa ulawulo oluphezulu kunokubhengeza umphunga. ²² Amanqanaba otywala egazi aye avavanywa ngokusebenzisa isampulu yomsila we-vein, kunye nexabiso le-ethanol (mL / h) kwigumbi le-vapor lahlengahlengiswa njengemfuneko ukuze kugcinwe amanqanaba egazi otywala kuluhlu lwe-125-250 mg / dL. Ababhali baqeshe iinkqubo zokusebenza ukuvavanya iinkuthazo zokuxhomekeka kotywala. Ukuvezwa kwe-Vapor kwandise iimpendulo zokusebenza kwe-10% w / v isiselo esinxilisayo xa iigundane zavavanywa nge-6-8 iiyure zokurhoxisa ngexesha leentsuku zokumamela ze-vapor. Izifundo zangaphambili zisebenzisa imodeli yokuphelisa yotywala engapheliyo ibonakalise ukuba iimpawu eziqinisekileyo zokuxhomekeka zikhona kwiigundane ngexesha lokurhoxa okukhulu, njengoko kubonakaliswa kukukhathazeka okufana nokuziphatha, ukwanda kotywala, kunye nokunyuka kokusebenzela ukusebenzela utywala kwangoko ngexesha lokuyeka kakhulu, nokuba izilwanyana zisenotywala egazini lazo ngenxa yokuvezwa komphunga. ^21-25 Zonke iimodeli zezilwanyana ukuxhomekeka kotywala, eneneni, yimodeli yamacandelo okuxhomekeka kotywala.

Imodeli yokubonisa umphunga inobuso obuthathaka, kuba izilwanyana zinyanzelwa ukuba zidle i-ethanol. Eyona nto inomdla wale modeli kukusebenza kwayo kwangaphambili (indlela imodeli yezilwanyana iqikelela ngayo iindlela kunye nonyango olunokubakho kwimeko yomntu). Umzekelo, i-acamprosate, ichiza elithintela ukubuya kwesiselo esinxilisayo ngokucinezelwa komnqweno, ngokunyanzelisa ukusela utywala ngamagundane enziwe axhomekeka etywaleni ngokufaka umphunga, kodwa hayi kulawulo olungathembekiyo olungakhange lubonakaliswe kumphunga wotywala. ²⁶

Ukuzilawula ngokwakho

Eyona nkqubo ithe ngqo yokuvavanya ukuqiniswa kwepropathi yento kukuvavanya ukuba izilwanyana ziya kusebenza (ngokubanzi, oku kuthetha ukuba uxinzelelo kumatshini wokushicilela) ukufumana into. Ukusetyenziswa kweemodeli zokuzilawula ngokwamachiza kufundiso lweziyobisi kusekwe kwingcinga yokuba iziyobisi zisebenza njengabaqinisi; Oko kukuthi, bonyusa ukubakho kokuziphatha okukhokelela kunikezelo lwabo. Ke, ukuzilawula ngokwamachiza kujongwa njengempendulo esebenzayo eqiniswa ziziphumo zeziyobisi, kwaye yinkqubo eqhelekileyo yokufunda ukuthathwa ngokuzithandela kweziyobisi kwizilwanyana zaselebhu. Ngaphantsi kwale nkqubo, isilwanyana senza impendulo, njengokucinezela i-lever, ehambisa idosi yeziyobisi. Kucingelwa ukuba iziyobisi zinokufana okusebenzayo kunye nezinye izinto zokuqinisa-njengokutya- eziye zafundwa ngokwesiko kwicandelo lokusebenza kwe-Skinner kwii-1930s. ²⁷

Imeko yokusebenza iyasetyenziselwa njengemodeli yezilwanyana yokusetyenziswa kweziyobisi ukususela kwii-1960s. Iiveki ²⁸ ichazwe, kwi-1962, indlela yokuzilawula ngaphakathi kwe-morphine kumgangatho. Ukusukela ngoko, ukuzilawula kuye kwaboniswa nge-heroin, ^29,30 icocaine, ^31-33 amphetamine, ³⁴ I-nicotine, ^35-37 ethanol, ^38-40 kunye ne-delta-9-THC. ⁴¹

Ukuzilawula ngaphakathi kwe-intravenous kuthathwa njengeyona ndlela inokuthenjwa yokuvavanywa kokuqiniswa kweziyobisi kwizilwanyana. ²⁷ Le ndlela ibonisa ubuso obuphakamileyo kunye nokuqinisekiswa kwangaphambili kokuvavanywa kokuqiniswa kweprophathi yokuqiniswa kwamachiza. Nangona kunjalo, uvandlakanyo lokungqinisisa ubunyani beemodeli zokuzilawula ekufumaneni iimpembelelo ezinokubakho zonyango lwezinto zonyango kunyango lweziyobisi lunqunyelwe ngenxa yokuba bambalwa kakhulu amayeza afumanekayo ukulungiselela le njongo, kwaye, okwangoku, phantse ngokupheleleyo Ukuthintela isiselo esinxilisayo okanye ukutshaya. ^1,27

Izixhobo ezisetyenziswa ekuqhubeni inkqubo yokulawula iziyobisi ekusebenzeni ziquka amagumbi afumanekayo kwezorhwebo abizwa ngokuba ziibhokisi zokusebenza okanye iibhokisi zeSkinner. Igumbi linepaneli enezixhobo ezicinezelwe sisilwanyana kwaye zidlulisele impendulo eyokuvula impompo yokungena kunye nokuhambisa idosi yesiyobisi. Ezinye iinkqubo ezisekwe kwezinye iimpendulo, ezinje ngokufaka impumlo ngeempuku okanye i-disk-pinging yehobe, nazo zingasetyenziswa. Ukuhanjiswa kwesiyobisi kunokuqulunqwa ukuze kudibane nokwenzeka kwezinye izehlo, ezinje ngezibane okanye iitoni, ezinokukhuthaza ucalucalulo kunye / okanye ukugxininiswa kwesibini. Ichiza lihlala lihanjiswa ngokusetyenziswa kwe-catheter ye-intravenous, nangona ezinye iindlela zinokusetyenziswa, njengendlela yomlomo we-ethanol okanye inhalation ye-nicotine. ^27,36

Ukuzilawula ngaphakathi kungenisa utyando lwecatheter kumthambo wejugular. I-catheter idluliswa ngokungxama kumqolo wempuku, apho iphuma khona kusiko oluncinci kwaye incanyathiselwe kumgangatho weplastiki onokufakwa ngaphakathi kwinkqubo yokubopha. Emva kotyando, izilwanyana ziyavunyelwa ukuba ziphinde zibuyele kwiintsuku ezininzi ezindlini zazo, ngokufikelela simahla ekutyeni nasemanzini, ngaphambi kokuqala kwenkqubo yokulungisa imeko. Umngxuma kuphahla lwamagumbi asebenzayo uvumela ukuhamba kunye nokuhamba simahla kwe-catheter ebotshelelwe, edityaniswe neswivel elingalinganiyo kunye nempompo yokumnika. ^27,36

Isigaba sokuqala sale modeli kukufumana indlela yokuziphatha. Ukuza kuthi ga ngoku, izilwanyana ziqeqeshelwa ukomeleza okuqhubekayo apho impendulo nganye (uxinzelelo lwe-lever) yomelezwa kukuhanjiswa kokufakwa kwesiyobisi (ukuzilawula ngaphakathi) okanye ithontsi lesisombululo (ukuzilawula ngomlomo). Ukufunyanwa kokuzilawula ngokwamachiza kuthathela ingqalelo imeko yokusingqongileyo kunye nekhemesti. Umzekelo, iCovington neMiczek ⁴² uxele ukuba inani elikhulu kakhulu leempuku ezazivezwe ngaphambili icocaine (15.0 mg / kg intraperitoneally, kube kanye ngosuku ngeentsuku ze-10) wafumana ukuzilawula kwe-cocaine kunokulawula izilwanyana ezifumene utyando ngealine.

Kwiparadigm yokuzilawula, ishedyuli yokuqhubela phambili (PR) isetyenziselwa ukuvavanya inkuthazo yokufumana ichiza. Ishedyuli ye-PR yokomeleza iyenziwa ngokunyuka kwenani leempendulo ezifunekayo ukufumana ukuhanjiswa kokufakwa kweziyobisi. Umzekelo, uRichardson kunye noRoberts ⁴³ icebise ialgorithm kulungiselelwa ukumiliselwa kwecocaine nganye ngokulandelelana kwayo ukuze kuveliswe uthotho lweemfuno zokuphendula eziza kuqala ngomlinganiso wazo kwaye zikhule ngokukhawuleza ngokwaneleyo ukuze umlinganiso ungadibani nenqobo yokuphendula ngokulandelelana ngaphakathi kwemizuzu engama-60, ngexesha leyure ezi-5 iseshoni. Ukuqhubela phambili komyinge ibingu-1, 2, 4, 6, 9, 12, 15, 20, 25, 32, 40, 50, 62, 77, 95, 118, 145, 178… Umndilili wokugqibela ogqityiweyo, okhokelela kumjikelo wokugqibela ukumnika, ichazwa njengendawo yokuqhekeka. Kwiprothokholi yokuzilawula, inqanaba lokophula phantsi kweeshedyuli ze-PR libonisa inkuthazo yesilwanyana ekuzilawuleni.

Kutshanje, sisebenzise ishedyuli ye-PR ukuvavanya ukuphakama okunokwenzeka kwindawo yokuqhekeka yokubonelela nge-nicotine efakwa ngaphakathi kwizilwanyana ezichazwe ngaphambili kuxinzelelo olwahlukileyo. Emva kwenqanaba lokufunyanwa kunye nolondolozo, ukuzilawula ngokwako ngokweshedyuli ye-PR yokuqiniswa kweziyobisi kwavavanywa. Ukuqhubela phambili kweemfuno zokuphendula kulandele i-algorithm 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26… Iigundane zazinemizuzu engama-60 yokugqibezela ngempumelelo umlinganiso ngamnye. Ukufakwa kokugqibela kokungeniswa kwachazwa njengendawo yokuphula. ^36,37 Kwisifundo sethu, iishedyuli ze-PR ziveze ukonyuka okukhulu kwamanqaku okuqhekezwa kweembambo ngaphambi kokuba kuvezwe uxinzelelo kulawulo, kucebisa ukuba ukuvezwa koxinzelelo kunokwandisa inkuthazo yokuzilawula ngokwakho. Ezi datha ziyahambelana nezinye iziphumo ezibonisa ukuba ukubonakaliswa kweziqendu ezine zoxinzelelo loxinzelelo kunyusa indawo yokuqhekezwa kwe-cocaine ngexesha leshedyuli ye-PR. ⁴² Ngokufanayo, kubonakalisiwe ukuba iigundane ezivezwe kuxinzelelo lweenyawo ezinyaweni zazinyusa iindawo zokuqhekezwa kwe-heroin malunga nolawulo lwazo. ⁴⁴

Iprotocol yokuzilawula nayo inokusetyenziselwa ukulinganisa iimpembelelo zokunyanzelwa kwamachiza phantsi kweemeko zokufikelela kwexesha elide (iiyure ze-24) kwishedyuli eqhubekayo yokuqinisa, eyaziwa ngokuba kukubhanqa. Iziphumo ezivela kwilabhoratri yethu zibonise ukuba ukubanjwa kwenkuku okwenziwe ngecocaine kukonyusa inicotine kwi-24-iyure ye-binge ye-nicotine ye-intravenous. ³⁷

Eyona nto ingalunganga kwiinkqubo zokuzilawula kukuba zichitha ixesha kwaye zibiza kakhulu xa kuthelekiswa nezinye iindlela. Ukongeza, izifundo zexesha elide zisebenzisa indlela yokungena kwiintonga zikhawulelwe ixesha lokufakwa kwe-catheters. ²⁷

Indawo yendawo

Kwinkqubo yokhetho olukhethiweyo, iziphumo zeli chiza, ezithathwa njengokusebenza ngokungavuseleliyo ngokunganyanzelisiyo (US), ziphindaphindwe zambini ngonyuselo lwangaphambili. Kule nkqubo, eyi-Pavlovian ngokwendalo, isikhuthazi esingathathi hlangothi sifumana amandla okwenza njengento ekhuthazayo (CS). Emva koko, le CS iya kukwazi ukwenza indlela yokuziphatha xa ichiza linempahla. Ezona ndlela zixhaphakileyo ezisetyenziselwa ukufundisisa ezikhethiweyo zisebenza kukhuthaza okusingqongileyo njenge-CS kwaye kubhekiswa kuzo njengendawo ekhethiweyo yendawo (CPP). Izixhobo zovavanyo lweparadigm ye-CPP zihlala zineebhokisi ezinamacandelo amabini ahlukileyo, ahlukaniswe yiminyango ye-guillotine, eyahlukileyo kubungakanani benyusa. Umzekelo, amaxinzelelo angahluka kumgangatho womgangatho, umbala wedonga, iipateni, okanye i-olonicory cices. ⁴⁵ Ikhomputha yesithathu (yokungathathi hlangothi) engazukudityaniswa ngechiza likwakhona ngesixhobo. ⁴⁶

Iprotocol yesiqhelo ye-CPP inezigaba ezithathu: imeko yangaphambili, imeko, kunye nemeko yangaphambili (uvavanyo). Kwinqanaba langaphambi kokulungisa imeko, isilwanyana ngasinye (iirati okanye iigundane) sibekwa kwigumbi elingathathwanga kunye neengcango zegilline zisuswe ukuze kuvunyelwe ukufikelela kuzo zonke izixhobo ze15 zemizuzu yeentsuku ze3. Ngomhla we-3, isilwanyana sibekwe kwizixhobo zokusebenza kunye nexesha elichithwe kwigumbi ngalinye lirekhodwa. Kwinqanaba lokubekwa phantsi kwemeko, iicarty zodwa zihlukaniswe yiminyango ye-guillotine kwaye isilwanyana esinye sifumana enye inaliti lechiza kunye nesithuthi sayo. Inaliti yeziyobisi libhanqwe ngecandelo elithile kwaye inaliti yesithuthi yenye eyenye. Ngokukhawuleza emva kwenaliti nganye, isilwanyana sivalelwe imizuzu eyi-30-40 kwigumbi elihambelanayo. Uvavanyo lokujonga imeko, isilwanyana sibekwe kwigumbi elingathathi hlangothi kunye neengcango ze-guillotine zisuswe ukuvumela ukufikelela kuzo zonke izixhobo. Ixesha elichithwe kwigumbi ngalinye lirekhodwa kwimizuzu ye-15 njengoko kuchaziwe kwisigaba sokumisela imeko yangaphambili; Uvavanyo lwenziwa kwimeko engenachiza. ⁴⁶ Ukonyuka kwexesha elichithwe kwigumbi lokubhangqa kunye nefuthe leziyobisi kubonisa ukuphuculwa kwe-CPP kwaye, ngenxa yoko, imiphumo yeso siyobisi.

I-CPP ixeliwe kuwo onke amachiza abangela ukuxhomekeka ebantwini; Nangona kunjalo, iziphumo zibambelele ngakumbi kwii-opiate nakwii-psychostimulants. ⁴⁵

Izifundo zezilwanyana zokuziphatha okuluthayo

Ukusetyenziswa kweemodeli ezichazwe apha ngasentla kukonyuse ngokucacileyo ukuqonda kwethu kwesiseko se-neurobiological sokuthatha iziyobisi. Nangona kunjalo, eyona nto iphambili kuphando lokusebenzisa iziyobisi kukujonga iindlela zokulutha. Iziyobisi ayisiyokuthatha iziyobisi kuphela, kodwa ulondolozo lokusetyenziswa kweziyobisi okunyanzelekileyo nangona zikho iziphumo ezibi. Ukuphulukana nolawulo kukhokelela ekusebenziseni iziyobisi ngaphezulu, kunyanzeliso lokufuna iziyobisi, kunye nokungakwazi ukuyeka ukusetyenziswa kwaso. Ke ngoko, kule minyaka idlulileyo, kwenziwa iinzame ezinkulu zokusebenzisa indlela yokuzilawula ukumisela imiba ethile yokuziphatha eyikhobokileyo kunokuphanda nje ukomeleza iziyobisi. Ngokukodwa, iinzame ziye zajongwa ukuba zichonge ukuba ingaba inkqubo ye-DSM-IV yokuxilongwa kweziyobisi inokuba yimodeli yesilwanyana. ²

Isifundo esibonisa ilizwe likaDeroche-Gamonet et al. ⁴⁷ ungumzekelo wesi sicwangciso esitsha sophando ngeziyobisi. Ababhali basebenzise ukuzilawula ngaphakathi kwe-cocaine ukuphanda ukuba ingaba ezinye izinto ezingamakhoboka zinokubonwa na kwiintonga. Babonisa ukuba indlela yokuziphatha efana neendlela ezintathu zokuqonda isifo (ubunzima bokuma okanye ukunciphisa umda wokungena iziyobisi; inkuthazo ephezulu yokuthatha eli chiza, ngemisebenzi egxile ekuthengweni nasekusetyenzisweni kwayo; kunye nokusetyenziswa kweziyobisi okuqhubekekayo ngaphandle kokuba kuneziphumo ezibi) imodareyithwe kumagundane aqeqeshelwe ukuzilawula i-cocaine.

Ukunyanzelwa kokusetyenziswa kweziyobisi luphawu lokutshintsha ukusuka ekusebenziseni iziyobisi ngamanye amaxesha. Ukufikelela ixesha elide (ukuntywila, bona ngentla) kuye kwasetyenziswa ngokubanzi ukubonisa ukwanda kokutya iziyobisi, ngakumbi icocaine kunye ne-ethanol. Amagundane ngokufikelela okwandisiweyo kukuzilawula iziyobisi ngokuthe ngcembe kukonyusa ukunxila kwawo ekuhambeni kweentsuku, ngendlela engahambelani ngokuthe ngqo nokunyamezelana. Umzekelo, iigundane ngokufikelela okwandisiweyo (iiyure ze-6 / zemini) ukuzilawula kwe-cocaine ngokuthe ngcembe ziyonyusa ukutya kwabo kwe-cocaine yonke imihla, ngelixa abo banokufikelela ngokulingeneyo kweziyobisi (iyure ye-1 / imini) bagcina amaxabiso azinzileyo okuzilawula ngokwamachiza, kwanasemva kokuba iinyanga ezininzi zovavanyo. ^48,49 Ukunyuka kokutya i-cocaine kunye nokufikelela okwandisiweyo kwesiyobisi esizilawulayo sele kunikwe ingxelo kwiingxelo ezininzi. ^50-52 Amadlala abonisa ukuzilawula okwandayo kwe-cocaine ikwabonisa ukonyusa okuchaphazela ichiza, njengoko kuboniswa ngokwanda kweendawo zokuphula ishedyuli ye-PR, ⁵³ efanekisela enye indlela yokuziphatha yokuzibandakanya.

Ukusetyenziswa kweziyobisi okunyanzelekileyo ngaphandle kwemiphumo emibi kuye kwenziwa kumzekelo wokufunda. Kwezi zifundo, indlela yokuziphatha okanye yokuthatha iziyobisi yapeyintwa ngokhuthazo olubi. Umzekelo, Vanderschuren et al. ⁵⁴ ibonakalise ukuba ukubhanxisa i-CS yohambayo (ukwetyisa iinyawo) ngolawulo lwecocaine yokucinezelela icinezela ekuziphatheni kweziyobisi kwiigundane ezinamava olawulo lwe-cocaine, kodwa hayi kumagundane ebelifumane ixesha elide kuthatha i-cocaine

Kwizifundo ezisebenzisa ukuntywila ngomlomo iziyobisi, ngakumbi i-ethanol, ukuthathwa kwesisombululo esine-quinine ekrakra isetyenziswa ngokuxhaphakileyo njengesivuseleli somlomo. ⁵⁵ Ukongezwa kwe-quinine kwisisombululo se-ethanol ebesikade sikhona kwiigundane kwiinyanga ze-3-4 akuzange kunciphise ukuthatha kwabo i-ethanol nangona incasa ekrakra ye-quinine. ⁵⁶ Ngokufanayo, u-Undercher et al. ⁵⁷ Kuxelwe ukuba iimpuku azizange zikwazi ukungazikhathaleli ii-quinine emva kokufikelela ixesha elide (iiveki ze-8) kwi-ethanol, njengoko zasela isixa esilinganayo se-ethanol kwiibhotile zinebhotolo ngaphandle komzimba.

Ubunzima ekuphepheni ekusebenziseni iziyobisi bukwabonakalisa ukuba likhoboka leziyobisi; Oku kungafundwa kwizilwanyana zaselebhu ngokuvavanya ukufuna iziyobisi kwimodeli yokuzilawula xa ichiza lingasashenxiswa ngokuphendula kumatshini wokushicilela wesilwanyana. Oku kuxhathisa ukupheliswa kwendlela yokusebenza yokusebenza kuye kwaqwalaselwa kwiigundane ezinembali yokufikelela okugqithisileyo kwi-heroin okanye i-cocaine self-management. ^47,58

Iziyobisi zineempawu zokuphazamiseka okungapheliyo. Ewe kunjalo, inani elininzi labantu abakhobokileyo babuyela ekuthatheni iziyobisi nasemva kwexesha lokurhoxa; Ke, imodeli yangaphambi kokubuyela umva ikwabalulekile kufundisiso lweendlela zokulutha. Ngale ndlela, de Wit & Stewart ⁵⁹ Yachaza ukuba ii-cocaine ezingezizo ezomdibaniselwano ze-cocaine okanye ukuboniswa kwakhona kwi-cocaine ene-cocaine ebuyelelene kwindlela yokuziphatha ecinezelayo kulandela ukupheliswa kwempendulo yomqhubi. Ngokusekwe kwezi ziphumo, bacebise ukuba imodeli yabo yokubuyiselwa isetyenziselwe ukufunda izinto ezibandakanyekayo ekubuyiselweni kokusetyenziswa kweziyobisi.

Iintlobo ezimbini zezilwanyana zibonakalise ziluncedo ekufundeni ukuphinda ubuye. ⁶⁰ Enye kukubuyiselwa kokuzilawula ngokwakho. ^61,62 Imodeli yesibini yovavanyo yokufunda ukubuyela kwizilwanyana kukubuyiselwa kwe-CPP. ^46,63,64 Kuleimodeli, izilwanyana ziqala ukuqeqeshwa ukuze zifumane impendulo ezinemeko, kwaye emva koko ziye zisiwe kwinkqubo yokupheliswa kwale ndlela yokuziphatha. Nje ukuba isimilo icinyiwe, ukusetyenziswa gwenxa kovavanyo (okt, ukubhengeza okuchasene neziyobisi okanye inkuthazo engeyiyo yeziyobisi) kuyabekwa kwaye kukhokelele ekuvuseleleni kwento eyayiqiniswe ngaphambili yokuziphatha. Ukufana okubonakalayo kwesi siphumo kunye nokuphinda ubuye kukhokelele ekusebenziseni le nkqubo njengemodeli yokubuyela umva kunye novavanyo lokukhanuka. ⁶⁰

Inqaku elifanelekileyo lemodeli yokubuyiselwa kwimeko yesiqhelo kukujonga ukuba izinto eziphinda ziphinde ziphinde zinqwenele abantu zinikwe ingxelo yokuba zibuyisela ukufuna iziyobisi kwizilwanyana zaselebhu. Ezi zinto zibandakanya ukuboniswa kwakhona kwichiza okanye iindlela ezinxulumene neziyobisi kunye nokuvezwa koxinzelelo. ^65,66

Ukuvezwa kwizigameko zoxinzelelo kuthathwa njengento enkulu enoxanduva lokubuyela iziyobisi kwakhona. ^67,68 Izifundo zaphambi kwexesha zibonise ukuba uxinzelelo lungabuyisela i-nicotine, icocaine, i-heroin, kunye ne-ethanol self-management. ^69-71 Ngokufanayo, izifundo ezininzi zibonise ukuba ukubonakaliswa koxinzelelo kubangela ukubuyiselwa kwe-opioid-, amphetamine-, cocaine-, kunye ne-nicotine-induced CPP. ^64,71-74

Kukho ubungqina obuvakalayo bokuxhasa ubunyani bobuso bemodeli yokubuyiselwa, kodwa akukho bungqina bayo bokubaluleka kwangaphambili okanye ukufana kokusebenza kwayo abusekelwanga ngokupheleleyo. ⁶⁰

Ukuqukumbela intetho

Olu hlaziyo lushwankathele iinkqubo ezithile ezisetyenziselwa uvavanyo lokuxhaphazwa kunye noxanduva lokuxhomekeka. Ezi ntlobo zemodeli yezilwanyana ziqashwe ngokubanzi ukufunda ngeendlela ze-neurobiological kunye neemolekyuli zokuthatha iziyobisi. Ngaphaya koko, inkqubela phambili yamva nje yokubonakalisa iimpawu zokungamakhoboka kwizifundo zezilwanyana, ngokusekwe kumgaqo-nkqubo weDSM-IV, inika ithuba elonwabisayo lokufunda ngemvelaphi kunye nemvelaphi yemfuza yokuthengisa iziyobisi. Ezi ndlela zintsha zikwazizixhobo ezilungileyo zokuphononongwa kweearhente zonyango ukuphucula iindlela zokulwa kwisigulana esikhoboka.

UCleopatra S. Planeta ngumntu ophandayo kaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Ucaphulo

1. I-Sanchis-Segura C, Spanagel R. Uvavanyo lokuziphatha ngokuqiniswa kweziyobisi kunye nezinto ezongelayo kwiintonga: isishwankathelo. Umlutha weBiol. I-2006; 11: 2-38. [ Links ]

2. IVanderschuren LJ, Ahmed SH. Izifundo zezilwanyana zokuziphatha okuluthayo. Cold Spring Harb Ukujonga uMedi. I-2013; 3: a011932. [ Links ]

3. I-Spanagel R, I-Zieglgansberger W. I-Anti-craving craving craving craving craving: izixhobo ezintsha ze-pharmacological ukufunda inkqubo yokulutha. Imikhwa yeHypacol Sci. I-1997; 18: 54-9. [ Links ]

4. I-Richter CP, iCampbell KH. Imigudu yokuNcamelela uTywala kunye nokuTyhilwa kweSisombululo esithandwa ziiRati. Inzululwazi. I-1940; 9: 507-8. [ Links ]

5. UTordoff MG, Bachmanov AA. Impembelelo yenani lotywala kunye neebhotile zamanzi kwi-murine alcohol alcohol. Utywala Iklinikhi Exp Res. I-2003; 27: 600-6. [ Links ]

6. IBoyle AE, uSmith BR, Spivak K, Amit Z. Ukusetyenziswa ngokuzithandela kwe-ethanol kwiigundane: ukubaluleka kwembonakalo yokubonisa ukubonakaliswa komgaqo wokufumana iziphumo zokugqibela. Behav Pharmacol. I-1994; 5: 502-12. [ Links ]

7. McBride WJ, Li TK. Iimodeli zezilwanyana ezinxilisayo: I-neurobiology yokuziphatha ephezulu yokusela utywala kwiintonga. I-Crit Rev Neurobiol. I-1998; 12: 339-69. [ Links ]

8. Leeman RF, Heilig M, Cunningham CL, Stephens DN, Duka T, O'Malley SS. Ukusetyenziswa kwe-ethanol: singayilinganisela njani? Ukufezekisa ukulungelelana phakathi kwabantu kunye nezilwanyana ze-phenotypes. Umlutha Biol. Ngo-2010; 15: 109-24. [ Links ]

9. IBell RL, uRodd ZA, uLumeng L, uMurphy JM, uMcBride WJ. Ukukhetha iirat ye-P kunye nemodeli yezilwanyana zokusela kakhulu. Umlutha weBiol. I-2006; 11: 270-88. [ Links ]

10. Crabbe JC, Metten P, Rhodes JS, Yu CH, brown LL, Phillips TJ, et al. Umgca weempuku ezikhethiweyo zokujolisa kwi-ethanol egazini ubonakalisa ukusela ebumnyameni ukuya kuhlobo lotywala. Ingqondo yebhayoloji. I-2009; 65: 662-70. [ Links ]

11. Ulumkile RA. Ukufunwa kwe-ethanol yokuzithandela kwiigundane kulandela ukubonakaliswa kwe-ethanol kwiishedyuli ezahlukeneyo. I-Psychopharmacologia. I-1973; 29: 203-10. [ Links ]

12. Crabbe JC, Harris RA, Koob GF. Izifundo zokuqala zesiselo esinxilisayo. Ann NY Acad Sci. I-2011; 1216: 24-40. [ Links ]

13. Crabbe JC, Phillips TJ, Belknap JK. Ubunzima bokuselwa kotywala: Izifundo kwiimodeli zemfuza zentlobo. Behav Genet. I-2010; 40: 737-50. [ Links ]

14. I-Lieber CS, uDe Carli LM. Ukuxhomekeka kwe-Ethanol kunye nokunyamezelana: imodeli yokulawulwa kwesondlo elawulwa kwi-rat. Res Commun Chem Pathol Pharmacol. I-1973; 6: 983-91. [ Links ]

15. UGilpin NW, uSmith AD, uCole M, Weiss F, uKob GF, uRichardson HN. Ukuziphatha kokusebenza kunye nenqanaba lotywala egazini kunye nengqondo yamagundane axhomekeke kuotywala. Utywala Iklinikhi Exp Res. I-2009; 33: 2113-23. [ Links ]

16. UFrye GD, uChapin RE, uVogel RA, iMailman RB, i-Kilts CD, uMueller RA, et al. Iziphumo zempatho ye-1,3-butanediol ebukhali kunye engapheliyo ekusebenzeni kwenkqubo ye-nervous system: uthelekiso ne-ethanol. J Theracol Exp Ther. I-1981; 216: 306-14. [ Links ]

17. I-Majchrowicz E. Ukungeniswa kokuxhomekeka komzimba kwi-ethanol kunye neendlela zokuziphatha ezichaphazelekayo kwiigundane. I-Psychopharmacologia. I-1975; 43: 245-54. [ Links ]

18. I-Lieber CS, iDeCarli LM. Izixa ezinconywayo zezondlo azizihoyisi iimpembelelo zetyhefu yethamo lotywala eligcina amanqanaba egazi e-ethanol. J Nutr. I-1989; 119: 2038-40. [ Links ]

19. UGoldstein DB, uPal N. Uxhomekeko lotywala obuveliswe kwiimpuku ngokuphefumla kwe-ethanol: ukulungiswa kwempendulo yokurhoxa. Inzululwazi. I-1971; 172: 288-90. [ Links ]

20. Rogers J, iWiener SG, Bloom FE. Iindlela zokuphatha i-ethanol yexesha elide kwiigundane: izibonelelo zokungenisa umoya ngaphakathi kwi-intubation okanye ekudleni okulwelo. I-Behav Neural Biol. I-1979; 27: 466-86. [ Links ]

21. IGilpin NW, iRichardson HN, uCole M, uKoob GF. Ukuqunjelwa kwevapor yotywala kwiigundane. I-Curr Protoc Neurosci. I-2008; Isahluko 9: Icandelo 9.29. [ Links ]

22. U-O'Dell LE, uRoberts AJ, uSmith RT, uKoob GF. Ukuphucula ukuzilawula kotywala emva kokungena ngokuthe rhoqo ngokuchaseneyo nokuvezwa komphunga kotywala. Utywala lweeNkcazo zoTywala. Ngo-2004; 28: 1676-82. [ Links ]

23. Funk CK, Zorrilla EP, Lee MJ, Rice KC, Koob GF. I-Corticotropin-ekhulula i-1 antagonists bakhetha ukunciphisa ukuzilawula kwe-ethanol kwiigundane ezixhomekeke kwi-ethanol. Ingqondo yebhayoloji. I-2007; 61: 78-86. [ Links ]

24. Roberts AJ, Cole M, Koob GF. I-Intra-amygdala muscimol iyanciphisa ukusebenza kwe-ethanol self-in rats ezixhomekeke kuzo. Utywala Iklinikhi Exp Res. I-1996; 20: 1289-98. [ Links ]

25. UValdez GR, uRobert AJ, uChan K, uDavis H, uBrennan M, uZorrilla EP, et al. Ukonyuka kokuzilawula kwe-ethanol kunye nokuziphatha okunexhala ngexesha lokurhoxiswa kwe-ethanol kunye nokuyeka okungapheliyo: ukulawulwa yinto ekhululayo ye-corticotropin. Utywala Iklinikhi Exp Res. I-2002; 26: 1494-501. [ Links ]

26. U-Magnen J, uTran G, uDurlach J, uMartin C. Ukuxhomekeka koxhomekeko kwiziselo ezinxilisayo zokuxakwa yi-Ca-acetyl homotaurinate. Utywala. I-1987; 4: 97-102. [ Links ]

27. IPanlilio LV, iGoldberg SR. Ukuzilawula kwamachiza kwizilwanyana nakubantu njengemodeli kunye nesixhobo sophando. Iziyobisi. I-2007; 102: 1863-70. [ Links ]

28. Iiveki JR. Uvavanyo lwe morphine yokuvavanya: indlela yokujova ngokuzenzekelayo inalitiyo kumagundane engathintelwanga. Inzululwazi. I-1962; 138: 143-4. [ Links ]

29. I-Bonese KF, i-Wainer BH, i-Fitch FW, i-Rothberg RM, i-Schuster CR. Utshintsho kulawulo lwe-heroin ngenkawu ye-rhesus emva kokugonywa kwe-morphine. Indalo. I-1974; 252: 708-10. [ Links ]

30. Pattison LP, McIntosh S, Budygin EA, Hemby SE. Ummiselo ohlukileyo wokuhanjiswa kwe-dopamine ye-accumbal kwii-rats ezilandela i-cocaine, i-heroin kunye nolawulo lwe-Speedball. J Neurochem. I-2012; 122: 138-46. [ Links ]

31. Hill SY, Powell BJ. I-cocoaine kunye ne-morphine self-management: Iziphumo zokukhulisa okwahlukileyo. IPhemacol Biochem Behav. I-1976; 5: 701-4. [ Links ]

32. UMiczek KA, uMchchler NH. Iziphumo ezisebenzayo zoxinzelelo lwentlalo kwi-IV cocaine ye-self-management kwiigundane. I-Psychopharmacology (Berl). I-1996; 128: 256-64. [ Links ]

33. Cruz FC, Quadros IM, Hogenelst K, Planeta CS, Miczek KA. Ukupheliswa koxinzelelo lwentlalo kumagundane: ukunyuka kwecocaine kunye "nebhola yesantya" ukuzilawula, kodwa hayi iqhawe. I-Psychopharmacology (Berl). I-2011; 215: 165-75. [ Links ]

34. Ukhetho R, Harris WC. Ukuzilawula kwe-d-amphetamine ngamagundane. I-Psychopharmacologia. I-1968; 12: 158-63. [ Links ]

35. IGoldberg SR, i-Spealman RD, iGoldberg DM. Ukuziphatha okuqhubekayo kumanani aphezulu agcinwa kukuzilawula kwe-nicotine. Inzululwazi. I-1981; 214: 573-5. [ Links ]

36. I-Leao RM, i-Cruz FC, iMarin MT, i-Planeta Cda S. Uxinzelelo lwenza uvakalelo lokuziphatha, yonyusa indlela yokuziphatha ekhangela i-nicotine kwaye ikhokelela ekunciphiseni kwe-CREB kwii-nucleus accumbens. IPhemacol Biochem Behav. I-2012; 101: 434-42. [ Links ]

37. Leao RM, Cruz FC, Carneiro-de-Oliveira PE, Rossetto DB, uValentini SR, Zanelli CF, et al. Ukuziphatha okuphuculweyo kwe-nicotine kulandela ukubonakaliswa kwangaphambili kwe-cocaine ephindaphindiweyo kuhamba kunye neenguqu kwi-BDNF kwii-nucleus accumbens zamagundane. IPhemacol Biochem Behav. I-2013; 104: 169-76. [ Links ]

38. USmith SG, uDavis WM. I-Intravenous alcohol-self-management kwi-rat. Isidumbu sePhemacol Res. I-1974; 6: 379-402. [ Links ]

39. UGrant KA, uSamson HH. Ukuzilawula ngomlomo kwe-ethanol kwiindawo zokutya kwamahhala. Utywala. I-1985; 2: 317-21. [ Links ]

40. Rob Robes AJ, Heyser CJ, Koob GF. Ukuzilawula okusebenzayo kwe-erryed kunye ne-ethanol engaphendulwanga: iziphumo kumanqanaba otywala egazi. Utywala Iklinikhi Exp Res. I-1999; 23: 1151-7. [ Links ]

41. IJustinova Z, iTanda G, iRedhi GH, iGoldberg SR. Ukuzilawula ngokwakho kwe-delta9-tetrahydrocannabinol (THC) ziinkawu zeekwayara ezinamachiza. I-Psychopharmacology (Berl). I-2003; 169: 135-40. [ Links ]

42. UCovington 3rd HE, uMiczek KA. Uxinzelelo oluphindaphindeneyo lokuhlulwa kwentlalo, i-cocaine okanye i-morphine. Iziphumo zokuvuselela uvakalelo ekuziphatheni ngokwakho kunye nokuzilawula kwe-cocaine ye-cocaine. I-Psychopharmacology (Berl). I-2001; 158: 388-98. [ Links ]

43. IRichardson NR, iRoberts DC. Ukuhlengahlengiswa komyinge weeshedyuli kwizifundo zokuzilawula iziyobisi kwiigundane: indlela yokuvavanya ukuqiniswa kokusebenza kakuhle. Iindlela zeJ Neurosci. I-1996; 66: 1-11. [ Links ]

44. UShaham Y, uStewart J. Ukudakumba koxinzelelo olucekeceke lonyusa ukuqina kokuzilawula kwe-heroin ye-intravenous kwiigundane. I-Psychopharmacology (Berl). I-1994; 114: 523-7. [ Links ]

45. Bardo MT, Bevins RA. Indawo ekhethiweyo kwindawo okhetha kuyo: yongeza ntoni ekuqondeni kwethu kwangaphambili komvuzo wamachiza? I-Psychopharmacology (Berl). I-2000; 153: 31-43. [ Links ]

46. Cruz FC, Leao RM, Marin MT, Planeta CS. Uxinzelelo lokuvuselela uxinzelelo lwe-amphetamine-ekhethiweyo yendawo ekhethiweyo kunye notshintsho kwi-tyrosine hydroxylase kwi-nucleus accumbens kwiigundana zokufikisa. IPhemacol Biochem Behav. I-2010; 96: 160-5. [ Links ]

47. UDeroche-Gamonet V, uBelin D, uPiazza PV. Ubungqina bokuziphatha-okufana nokuziphatha kumlinganiso. Inzululwazi. I-2004; 305: 1014-7. [ Links ]

48. Ahmed SH, Koob GF. Inguqu ukusuka kokumodareyitha ukuya nokufumana kakhulu iziyobisi: utshintsho kwincopho ye-hedonic. Inzululwazi. I-1998; 282: 298-300. [ Links ]

49. Ahmed SH, Koob GF. Ukunyuka okungapheliyo kwindawo yokumisela ye-cocaine yokuzilawula emva kokunyuka kwamagundane. I-Psychopharmacology (Berl). I-1999; 146: 303-12. [ Links ]

50. UBen-Shahar O, uPosthumus EJ, uWaldroup SA, uEttenberg A. Uphakamile ukufuna iziyobisi kulandela ukufikelela okwandisiweyo kwemihla ngemihla kwi-cocaine elawula ukuzilawula. Iprog Neuropsychopharmacol Biol Psychiatry. I-2008; 32: 863-9. [ Links ]

51. I-Quadros IM, Miczek KA. Iindlela ezimbini zokuxinana kakhulu kwe-cocaine: ukunyuka okunyamezelayo emva koxinzelelo lokwahlula intlalontle kunye nokunyuka kwenqanaba lokutya ngenxa yemeko yokufikelela eyandisiweyo kumagundane. I-Psychopharmacology (Berl). I-2009; 206: 109-20. [ Links ]

52. U-Ewe Y, uMartin-Fardon R, u-Weiss F. oziphatha kunye nobungqina bokusebenza kwe-metabotropic glutamate receptor 2 / 3 kunye ne-metabotropic glutamate receptor 5 dysregulation in racacine-ascorated rats: factor in the transition toxhomekeka. Ingqondo yebhayoloji. I-2010; 68: 240-8. [ Links ]

53. I-Liu Y, iRoberts DC, iMorgan D. Iziphumo zokufezekisa ukuzilawula kunye nokuhlutshwa kwiindawo zokugcina ezigcinwe yi-cocaine kumagundane. I-Psychopharmacology (Berl). I-2005; 179: 644-51. [ Links ]

54. IVanderschuren LJ, i-everitt BJ. Ukufuna iziyobisi kuyanyanzeleka emva kokuzilawula ixesha elide kwecocaine. Inzululwazi. I-2004; 305: 1017-9. [ Links ]

55. I-Wolffgraphm J. Indlela ye-ethopharmacological ekuphuhlisweni kweziyobisi. I-Neurosci Biobehav Rev. 1991; 15: 515-9. [ Links ]

56. I-Hopf FW, i-Chang SJ, iSparta DR, i-Bowers MS, uBonci A. Inkuthazo yotywala iye yanyamezelana nokukrexeza kwe-quinine emva kwe-3 ukuya kwi-4 iinyanga zokuzilawula. Utywala Iklinikhi Exp Res. I-2010; 34: 1565-73. [ Links ]

57. I-HMB encinci, i-Van Kerkhof LWM, iVanderschuren LJMJ. Utywala olungaguqukiyo nolungenamdla kwiintwala zesilisa. Utywala Iklinikhi Exp Res. I-2010; 34: 1219-25. [ Links ]

58. Ahmed SH, Walker JR, Koob GF. Ukuqhubeka kokunyusa kwinkuthazo yokuthatha i-heroin kumagundane enembali yokunyuka kweziyobisi. I-Neuropsychopharmacology. I-2000; 22: 413-21. [ Links ]

59. de Wit H, Stewart J. Ukugxininiswa kwakhona kwe-cocaine-kokuqiniswa kokuphendula kumqolo. I-Psychopharmacology (Berl). I-1981; 75: 134-43. [ Links ]

60. Katz J, Higgins S. Ukunyaniseka komzekelo wokubuyisela kunye nokunqwenela ukuphinda usebenzise iziyobisi. I-Psychopharmacology (Berl). I-2003; 168: 21-30. [ Links ]

61. UShaham Y, uRajabi H, uStewart J. Buyela ekufuneni i-heroin kumagundane phantsi kwesondlo se-opioid: Iziphumo zoxinzelelo, i-heroin priming, kunye nokurhoxa. J Neurosci. I-1996; 16: 1957-63. [ Links ]

62. UShaham Y, Adamson LK, Grocki S, Corrigall WA. Ukuvuselelwa kunye nokuvuselela okuzenzekelayo kwe-nicotine efuna kumagundane. I-Psychopharmacology (Berl). I-1997; 130: 396-403. [ Links ]

63. I-Mueller D, uStewart J. Cocaine-ofakwe indawo ekhethiweyo: ukubuyisela kwakhona ngokungenisa inaliti yecocaine emva kokutshabalala. Behav Brain Res. I-2000; 115: 39-47. [ Links ]

64. URibeiro Do Couto B, Aguilar MA, Manzanedo C, Rodriguez-Arias M, Armario A, Minarro J. Uxinzelelo lwentlalo lusebenza njengoxinzelelo lomzimba ekubuyiseleni ukuthanda indawo ye-morphine. I-Psychopharmacology (Berl). I-2006; 185: 459-70. [ Links ]

65. I-Chiamulera C, i-Borgo C, i-Falchetto S, uValerio E, uTessari M. Nicotine ukuphinda azilawule kwi-nicotine self-management emva kwexesha elide. I-Psychopharmacology (Berl). I-1996; 127: 102-7. [ Links ]

66. I-Aguilar MA, iRodriguez-Arias M, iMinarro J. Neurobiological yeendlela zokuphinda zikhethwe indawo ekhethwe phantsi kweziyobisi. I-Brain Res Rev 2009; 59: 253-77. [ Links ]

67. USinha R. Uxinzelelo luyonyusa njani ingozi yokusetyenziswa gwenxa kweziyobisi nokubuyela umva? I-Psychopharmacology (Berl). I-2001; 158: 343-59. [ Links ]

68. USinha R, uGarcia M, uPaliwal P, uKreek MJ, eRounsaville BJ. Uxinzelelo lwe-cocaine olunomdla woxinzelelo kunye neempendulo ze-hypothalamic-pituitary-pituitary-adrenal zixela kwangaphambili ukubuyela kwesiphumo se-cocaine. Ingqondo yeArch Gen Psychiatry. I-2006; 63: 324-31. [ Links ]

69. IBuczek Y, Le AD, uWang A, uStewart J, uShaham Y. Uxinzelelo luvuselela ukukhangela i-nicotine kodwa kungabi sisisombululo sokufuna kumagundane. I-Psychopharmacology (Berl). I-1999; 144: 183-8. [ Links ]

70. UShaham Y, Erb S, uStewart J. Uxinzelelo-oluvuselelekayo kwi-heroin kunye ne-cocaine efuna iigundane: uphononongo. I-Brain Res Brain Res Rev 2000; 33: 13-33. [ Links ]

71. USchank JR, uKhetho weCL, iRowe KE, uCheng K, iThorsell A, iRice KC, et al. Uxinzelelo olubuyiselwe kukufuna utywala kwiigundane kukhethwa ngokunyanzelwa yi-neurokinin 1 (NK1) antagonist L822429. I-Psychopharmacology (Berl). I-2011; 218: 111-9. [ Links ]

72. Cruz FC, Marin MT, Planeta CS. Ukubuyiselwa kwakhona kokukhethwa kwindawo ye-amphetamine kuthathe ixesha elide kwaye kuhambelana nokuncipha kokuchazwa kwee-receptors ze-AMPA kwi-nucleus accumbens. I-Neuroscience. I-2008; 151: 313-9. [ Links ]

73. I-Redila VA, i-Chavkin C. Ukuvuselelwa koxinzelelo lokufuna icocaine kuhambelana nenkqubo ye-kappa opioid. I-Psychopharmacology (Berl). I-2008; 200: 59-70. [ Links ]

74. I-Leao RM, i-Cruz FC, i-Planeta CS. Ukuvezwa koxinzelelo olukhulu kakhulu lokuthintela umxhelo kubuyisela i-nicotine-in ind end place preference in rats. Behav Pharmacol. I-2009; 20: 109-13. [ Links ]

Imbalelwano: CleopatraS. I-Planeta, iRodovia Araraquara-Jaú, km ye-01, ye-CEP 14801-902, eAraraquara, SP, eBrazil. I-imeyile: [imeyile ikhuselwe]

ukuxela Ababhali babika ingxabano yomdla.